Obesity and the cerebral microvascular responses to ischemic stroke

Abstract

Obesity is a well-documented and modifiable risk factor for ischemic stroke. We tested the hypothesis that obesity exacerbates the microvascular dysfunction and brain damage induced by ischemia-reperfusion (I/R). Middle cerebral artery occlusion (30 min) and reperfusion was induced in wild type (WT) and leptin-deficient ob/ob mice. The adhesion of leukocytes (LA) and platelets (PA) in postischemic cerebral venules was monitored after 4 hrs of reperfusion by intravital microscopy. Infarct volume was estimated from brain slices (obtained 24 hrs after reperfusion) using the TTC staining method. Blood-brain barrier dysfunction was quantified using the Evans blue (EB) method. Brain water (WC) content was determined as (wet weight–dry weight)/wet weight (%). I/R elicited significant increases in LA (116 ± 82 vs 308 ± 202 cells/mm2) and PA in cerebral venules of both WT and ob/ob mice, however the responses were exaggerated in ob/ob mice. A similar pattern of I/R-induced increases in infarct volume (16.4 ± 6.0 vs 27.6 ± 3.2 %), EB extravasation (0.013 ± 0.0082 vs 0.031 ± 0.012), and WC (79.8 ± 0.62 vs 81.3 ± 0.31%) was noted in WT and ob/ob mice, with the latter group exhibiting more profound changes. These findings indicate that the microvascular dysfunction and brain injury after I/R is exaggerated in ob/ob mice and that obesity leads to greater morbidity following ischemic stroke. (HL26441)